Hachim Asmaa, Gu Haogao, Kavian Otared, Kwan Mike Yw, Chan Wai-Hung, Yau Yat Sun, Chiu Susan S, Tsang Owen Ty, Hui David Sc, Ma Fionn, Lau Eric Hy, Cheng Samuel Ms, Poon Leo Lm, Peiris Js Malik, Valkenburg Sophie A, Kavian Niloufar
HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Division of Public Health Laboratory Sciences, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
medRxiv. 2021 Jan 4:2021.01.03.21249180. doi: 10.1101/2021.01.03.21249180.
Children are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed.
We tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS).
Children have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.
与成人相比，儿童受严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的临床影响较小，大多数病例为轻症或无症状，而感染结果的差异尚不清楚。抗体反应的动力学、强度和格局可能会影响2019冠状病毒病（COVID-19）的临床严重程度和血清学诊断。因此，需要对儿童和成人的抗体格局进行全面调查。
我们检测了香港122例有症状和无症状SARS-CoV-2感染儿童在症状出现后长达206天的254份血浆，其中包括来自58名儿童的146份纵向样本。纳入成人COVID-19患者和疫情前的对照进行比较。我们通过荧光素酶免疫沉淀系统（LIPS）评估了针对一组14种SARS-CoV-2结构和辅助蛋白的抗体。
儿童的刺突蛋白和核衣壳蛋白抗体水平低于成人，其累积体液反应更多地扩展到辅助蛋白（非结构蛋白1（NSP1）和开放阅读框（ORF））。使用三种核衣壳蛋白、ORF3b、ORF8抗体进行的敏感血清学检测可以区分儿童中的COVID-19。主成分分析揭示了儿童独特的血清学特征，对变异贡献最大的是对非结构蛋白ORF3b、NSP1、ORF7a和ORF8的反应。纵向采样显示，除了呈下降趋势的ORF7b抗体外，抗体至少维持或增加了6个月。值得注意的是，儿童对已知的干扰素拮抗剂（ORF3b、ORF6和ORF7a）有更高的抗体反应。儿童中多样化的SARS-CoV-2抗体反应可能是推动控制SARS-CoV-2感染的一个重要因素。
